Architectural control of metabolic plasticity in epithelial cancer cells

Metabolic plasticity enables cancer cells to switch between glycolysis and oxidative phosphorylation to adapt to changing conditions during cancer progression, whereas metabolic dependencies limit plasticity. To understand a role for the architectural environment in these processes we examined metabolic dependencies of cancer cells cultured in flat (2D) and organotypic (3D) environments. Here we show that cancer cells in flat cultures exist in a high energy state (oxidative phosphorylation), are glycolytic, and depend on glucose and glutamine for growth. In contrast, cells in organotypic culture exhibit lower energy and glycolysis, with extensive metabolic plasticity to maintain growth during glucose or amino acid deprivation. Expression of KRASG12V in organotypic cells drives glucose dependence, however cells retain metabolic plasticity to glutamine deprivation. Finally, our data reveal that mechanical properties control metabolic plasticity, which correlates with canonical Wnt signaling. In summary, our work highlights that the architectural and mechanical properties influence cells to permit or restrict metabolic plasticity.

Evolution of Carbides during Prestrain and Tempering

The effect of thermo-mechanical treatment on the microstructural evolution of low carbon micro-alloyed high strength steel was studied by combining prestrain with tempering (PST) in this paper. It was found that the prestrain causes the dislocation to plug up around the grain boundary and carbide, resulting in carbide boundary fragmentation. Moreover, it breaks the thermo-dynamic equilibrium between the matrix and carbide, induces the dissolution of carbon in the high energy state, and then changes the distribution of carbon in the matrix. In the subsequent tempering process, the precipitation regularity of carbide was changed, which promoted the precipitation carbide at low temperature. The influence of carbide precipitation on dislocation can be divided into two stages: the first stage was precipitation induced creep, which promoted stress relaxation; the second stage was precipitation pinning dislocation, which improved material strength and inhibited stress relaxation.

Giant vortex clusters in a two-dimensional quantum fluid

Adding energy to a system through transient stirring usually leads to more disorder. In contrast, point-like vortices in a bounded two-dimensional fluid are predicted to reorder above a certain energy, forming persistent vortex clusters. In this study, we experimentally realize these vortex clusters in a planar superfluid: a 87Rb Bose-Einstein condensate confined to an elliptical geometry. We demonstrate that the clusters persist for long time periods, maintaining the superfluid system in a high-energy state far from global equilibrium. Our experiments explore a regime of vortex matter at negative absolute temperatures and have relevance for the dynamics of topological defects, two-dimensional turbulence, and systems such as helium films, nonlinear optical materials, fermion superfluids, and quark-gluon plasmas.

A high-energy-state biomimetic enzyme of oxygen-deficient MnTiO3 nanodiscs for sensitive electrochemical sensing of the superoxide anion

A high-energy-state biomimetic enzyme for the superoxide anion is presented by inducing surface oxygen defects in MnTiO3 nanodiscs.

Stimulation of cyclic electron flow around PSI as a response to the combined stress of high light and high temperature in grape leaves

Changes in cyclic electron flow (CEF) around PSI activity after exposing grape (Vitis vinifera L.) seedling leaves to the combined stress of high temperature (HT) and high light (HL) were investigated. The PSII potential quantum efficiency (Fv/Fm) decreased significantly under exposure to HT, and this decrease was greater when HT was combined with HL, whereas the PSI activity maintained stable. HT enhanced CEF mediated by NAD(P)H dehydrogenase remarkably. Compared with the control leaves, the half-time of P700+ re-reduction decreased during the HT treatment; this decrease was even more pronounced under the combined stress, implying significantly enhanced CEF as a result of the treatment. However, the heat-induced increase in nonphotochemical quenching (NPQ) was greater under HL, accompanied by a greater enhancement in high-energy state quenching. These results suggest that the combined stress of HT and HL resulted in severe PSII photoinhibition, whereas CEF showed plasticity in its response to environmental stress and played an important role in PSII and PSI photoprotection through accelerating generation of the thylakoid proton gradient and the induction of NPQ.

Structural basis for ligand binding to an enzyme by a conformational selection pathway

Proteins can bind target molecules through either induced fit or conformational selection pathways. In the conformational selection model, a protein samples a scarcely populated high-energy state that resembles a target-bound conformation. In enzymatic catalysis, such high-energy states have been identified as crucial entities for activity and the dynamic interconversion between ground states and high-energy states can constitute the rate-limiting step for catalytic turnover. The transient nature of these states has precluded direct observation of their properties. Here, we present a molecular description of a high-energy enzyme state in a conformational selection pathway by an experimental strategy centered on NMR spectroscopy, protein engineering, and X-ray crystallography. Through the introduction of a disulfide bond, we succeeded in arresting the enzyme adenylate kinase in a closed high-energy conformation that is on-pathway for catalysis. A 1.9-Å X-ray structure of the arrested enzyme in complex with a transition state analog shows that catalytic sidechains are properly aligned for catalysis. We discovered that the structural sampling of the substrate free enzyme corresponds to the complete amplitude that is associated with formation of the closed and catalytically active state. In addition, we found that the trapped high-energy state displayed improved ligand binding affinity, compared with the wild-type enzyme, demonstrating that substrate binding to the high-energy state is not occluded by steric hindrance. Finally, we show that quenching of fast time scale motions observed upon ligand binding to adenylate kinase is dominated by enzyme–substrate interactions and not by intramolecular interactions resulting from the conformational change.